Annotation for this protein is in progress - please check future releases for more complete information


DP00086: Cellular tumor antigen p53FASTA viewXML view

General information
DisProt:DP00086
Name:Cellular tumor antigen p53
Synonym(s):P53_HUMAN
Tumor suppressor p53
Oncoprotein p53
Phosphoprotein p53
p53 transformation suppressor
Transformation-related protein 53
TRP53
Antigen NY-CO-13
First appeared in release:Release 1.0 (08/01/2003)
UniProt:P04637
UniGene:Hs.654481
SwissProt: P53_HUMAN
TrEMBL:  
NCBI (GI): 269849759
Source organism:Homo sapiens (Human)
Sequence length:393
Percent disordered:29%
Homologues: 


Native sequence

        10         20         30         40         50         60
         |          |          |          |          |          |
MEEPQSDPSV EPPLSQETFS DLWKLLPENN VLSPLPSQAM DDLMLSPDDI EQWFTEDPGP - 60
DEAPRMPEAA PPVAPAPAAP TPAAPAPAPS WPLSSSVPSQ KTYQGSYGFR LGFLHSGTAK - 120
SVTCTYSPAL NKMFCQLAKT CPVQLWVDST PPPGTRVRAM AIYKQSQHMT EVVRRCPHHE - 180
RCSDSDGLAP PQHLIRVEGN LRVEYLDDRN TFRHSVVVPY EPPEVGSDCT TIHYNYMCNS - 240
SCMGGMNRRP ILTIITLEDS SGNLLGRNSF EVRVCACPGR DRRTEEENLR KKGEPHHELP - 300
PGSTKRALPN NTSSSPQPKK KPLDGEYFTL QIRGRERFEM FRELNEALEL KDAQAGKEPG - 360
GSRAHSSHLK SKKGQSTSRH KKLMFKTEGP DSD



Functional narrative    

Cellular tumor antigen p53 is essential for the regulation of the cell cycle and apoptosis. P53 coordinates DNA repair processes. P53 is an important protein for cancer progression as it has a high mutation rate and inactivation of P53 has been linked to most forms of cancer.

Region 2: 15-16 Region 3: 27-29 Region 1: 1-73 Region 4: 183-188 Region 5: 200-200 Region 6: 224-227 Region 7: 291-312 Region 8: 319-323 Region 9: 357-360

Map of ordered and disordered regions







Note: 'Mouse' over a region to see the start and stop residues. Click on a region to see detailed information.


Region 1
Type:Disordered - Extended
Name: 
Location:1 - 73
Length:73
Region sequence:

MEEPQSDPSVEPPLSQETFSDLWKLLPENNVLSPLPSQAMDDLMLSPDDIEQWFTEDPGP
DEAPRMPEAAPPV

Modification type: Engineered
Fragment
PDB:  
Structural/functional type: Function arises from the disordered state
Functional classes: Molecular recognition effectors
Functional subclasses: Unknown
Detection methods:
  1. Circular dichroism (CD) spectroscopy, near-UV (pH: 6.1; Phosphate Buffer; TFE)
References:
  1. Chang J, Kim DH, Lee SW, Choi KY, Sung YC. "Transactivation ability of p53 transcriptional activation domain is directly related to the binding affinity to TATA-binding protein." J Biol Chem. 1995; 270(42): 25014-9. PubMed: 7559631
Comments:
This disordered region was discovered in an engineered fragment containing residues 1-73.


Region 2
Type:Disordered - Extended
Name: 
Location:15 - 16
Length:2
Region sequence:

SQ

Modification type: Complex
Engineered
Fragment
PDB:  
Structural/functional type: Function arises from the disordered state
Functional classes: Unknown
Functional subclasses: Unknown
Detection methods:
  1. X-ray crystallography (308 K; MDM2)
References:
  1. Kussie PH, Gorina S, Marechal V, Elenbaas B, Moreau J, Levine AJ, Pavletich NP. "Structure of the MDM2 oncoprotein bound to the p53 tumor suppressor transactivation domain." Science. 1996; 274(5289): 948-53. PubMed: 8875929
Comments:
This disordered region was discovered in an engineered fragment containing residues 15-29.


Region 3
Type:Disordered - Extended
Name: 
Location:27 - 29
Length:3
Region sequence:

PEN

Modification type: Complex
Engineered
Fragment
PDB:  
Structural/functional type: Function arises from the disordered state
Functional classes: Unknown
Functional subclasses: Unknown
Detection methods:
  1. X-ray crystallography (308 K; MDM2)
References:
  1. Kussie PH, Gorina S, Marechal V, Elenbaas B, Moreau J, Levine AJ, Pavletich NP. "Structure of the MDM2 oncoprotein bound to the p53 tumor suppressor transactivation domain." Science. 1996; 274(5289): 948-53. PubMed: 8875929
Comments:
The protein studied was an engineered fragment containing residues 15-29.


Region 4
Type:Disordered - Extended
Name: 
Location:183 - 188
Length:6
Region sequence:

SDSDGL

Modification type: Engineered
Fragment
PDB: 1GZH:A
Structural/functional type: Relationship to function unknown
Functional classes: Unknown
Functional subclasses: Unknown
Detection methods:
  1. X-ray crystallography
References:
  1. Derbyshire DJ, Basu BP, Date T, Iwabuchi K, Doherty AJ. "Purification, crystallization and preliminary X-ray analysis of the BRCT domains of human 53BP1 bound to the p53 tumour suppressor." Acta Crystallogr D Biol Crystallogr. 2002; 58(Pt 10 Pt 2): 1826-9. PubMed: 12351827

  2. Derbyshire DJ, Basu BP, Serpell LC, Joo WS, Date T, Iwabuchi K, Doherty AJ. "Crystal structure of human 53BP1 BRCT domains bound to p53 tumour suppressor." EMBO J. 2002; 21(14): 3863-72. PubMed: 12110597
Comments:
The disordered region characterized was studied in an engineered fragment containing residues 95-292.


Region 5
Type:Disordered - Extended
Name: 
Location:200 - 200
Length:1
Region sequence:

N

Modification type: Engineered
Fragment
PDB: 1GZH:A
Structural/functional type: Relationship to function unknown
Functional classes: Unknown
Functional subclasses: Unknown
Detection methods:
  1. X-ray crystallography
References:
  1. Derbyshire DJ, Basu BP, Date T, Iwabuchi K, Doherty AJ. "Purification, crystallization and preliminary X-ray analysis of the BRCT domains of human 53BP1 bound to the p53 tumour suppressor." Acta Crystallogr D Biol Crystallogr. 2002; 58(Pt 10 Pt 2): 1826-9. PubMed: 12351827

  2. Derbyshire DJ, Basu BP, Serpell LC, Joo WS, Date T, Iwabuchi K, Doherty AJ. "Crystal structure of human 53BP1 BRCT domains bound to p53 tumour suppressor." EMBO J. 2002; 21(14): 3863-72. PubMed: 12110597
Comments:
The disordered region characterized was studied in an engineered fragment containing residues 95-292.




Region 6
Type:Disordered - Extended
Name: 
Location:224 - 227
Length:4
Region sequence:

EVGS

Modification type: Engineered
Fragment
PDB: 1GZH:A
Structural/functional type: Relationship to function unknown
Functional classes: Unknown
Functional subclasses: Unknown
Detection methods:
  1. X-ray crystallography
References:
  1. Derbyshire DJ, Basu BP, Date T, Iwabuchi K, Doherty AJ. "Purification, crystallization and preliminary X-ray analysis of the BRCT domains of human 53BP1 bound to the p53 tumour suppressor." Acta Crystallogr D Biol Crystallogr. 2002; 58(Pt 10 Pt 2): 1826-9. PubMed: 12351827

  2. Derbyshire DJ, Basu BP, Serpell LC, Joo WS, Date T, Iwabuchi K, Doherty AJ. "Crystal structure of human 53BP1 BRCT domains bound to p53 tumour suppressor." EMBO J. 2002; 21(14): 3863-72. PubMed: 12110597
Comments:
The disordered region characterized was studied in an engineered fragment containing residues 95-292.




Region 7
Type:Disordered - Extended
Name: 
Location:291 - 312
Length:22
Region sequence:

KKGEPHHELPPGSTKRALPNNT

Modification type: Engineered
Fragment
Mutant
PDB: 1UOL:A
Structural/functional type: Relationship to function unknown
Functional classes: Unknown
Functional subclasses: Unknown
Detection methods:
  1. X-ray crystallography
References:
  1. Joerger AC, Allen MD, Fersht AR. "Crystal structure of a superstable mutant of human p53 core domain. Insights into the mechanism of rescuing oncogenic mutations." J Biol Chem. 2004; 279(2): 1291-6. PubMed: 14534297
Comments:
The disordered region characterized was from an engineered fragment containing residues 94-312 and mutations at M133L, V203A, N239Y, N268D.


Region 8
Type:Disordered - Extended
Name: 
Location:319 - 323
Length:5
Region sequence:

KKKPL

Modification type: Engineered
Fragment
PDB: 1OLG:A, 1OLH:A, 1SAE:A, 1SAE:B, 1SAE:C, 1SAE:D, 1SAF:A, 1SAF:B, 1SAF:C, 1SAF:D, 1SAG:A, 1SAG:B, 1SAG:C, 1SAG:D, 1SAH:A, 1SAH:B, 1SAH:C, 1SAH:D, 1SAI:A, 1SAI:B, 1SAI:C, 1SAI:D, 1SAK:A, 1SAK:B, 1SAK:C, 1SAK:D, 1SAL:A, 1SAL:B, 1SAL:C, 1SAL:D, 3SAK:A, 3SAK:B, 3SAK:C, 3SAK:D
Structural/functional type: Function arises from the disordered state
Functional classes: Unknown
Functional subclasses: Unknown
Detection methods:
  1. Nuclear magnetic resonance (NMR)
References:
  1. Kuszewski J, Gronenborn AM, Clore GM. "Improving the packing and accuracy of NMR structures with a pseudopotential for the radius of gyration." J Am Chem Soc. 1999; 121(10): 2337-8.
Comments:
 



Region 9
Type:Disordered - Extended
Name: 
Location:357 - 360
Length:4
Region sequence:

KEPG

Modification type: Engineered
Fragment
PDB: 1OLG:A, 1OLH:A, 1SAE:A, 1SAE:B, 1SAE:C, 1SAE:D, 1SAF:A, 1SAF:B, 1SAF:C, 1SAF:D, 1SAG:A, 1SAG:B, 1SAG:C, 1SAG:D, 1SAH:A, 1SAH:B, 1SAH:C, 1SAH:D, 1SAI:A, 1SAI:B, 1SAI:C, 1SAI:D, 1SAK:A, 1SAK:B, 1SAK:C, 1SAK:D, 1SAL:A, 1SAL:B, 1SAL:C, 1SAL:D, 3SAK:A, 3SAK:B, 3SAK:C, 3SAK:D
Structural/functional type: Function arises from the disordered state
Functional classes: Unknown
Functional subclasses: Unknown
Detection methods:
  1. Nuclear magnetic resonance (NMR)
References:
  1. Kuszewski J, Gronenborn AM, Clore GM. "Improving the packing and accuracy of NMR structures with a pseudopotential for the radius of gyration." J Am Chem Soc. 1999; 121(10): 2337-8.
Comments:
This disordered region was located in an engineered fragment containing residues 319-360.


References

  1. Huang F, Rajagopalan S, Settanni G, Marsh RJ, Armoogum DA, Nicolaou N, Bain AJ, Lerner E, Haas E, Ying L, Fersht AR. "Multiple conformations of full-length p53 detected with single-molecule fluorescence resonance energy transfer." Proc Natl Acad Sci U S A. 2009. PubMed: 19933326

  2. Sharma AK, Ali A, Gogna R, Singh AK, Pati U. "p53 Amino-terminus region (1-125) stabilizes and restores heat denatured p53 wild phenotype." PLoS One. 2009; 4(10): e7159. PubMed: 19847292

  3. Soussi T, Caron de Fromentel C, May P. "Structural aspects of the p53 protein in relation to gene evolution." Oncogene. 1990; 5(7): 945-52. PubMed: 2142762

  4. Tidow H, Melero R, Mylonas E, Freund SM, Grossmann JG, Carazo JM, Svergun DI, Valle M, Fersht AR. "Quaternary structures of tumor suppressor p53 and a specific p53 DNA complex." Proc Natl Acad Sci U S A. 2007; 104(30): 12324-9. PubMed: 17620598


If you have any comments or wish to provide additional references to this protein or its disordered region(s), please click here to e-mail us.


Disprot-footer
Contact us